The developmental stages of osteoblast growth and differentiation exhibit selective responses of genes to growth factors (TGF beta 1) and hormones (vitamin D and glucocorticoids).
The developmental stages of osteoblast growth and differentiation exhibit selective responses of genes to growth factors (TGF beta 1) and hormones (vitamin D and glucocorticoids).
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发表时间：
1993
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通讯作者：
J. Lian;G. Stein
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作者：
J. Lian;G. Stein
成骨细胞在体外经历生长和分化的发育序列，其特征是细胞生长和骨相关基因的阶段特异性表达。我们的研究表明，对成骨细胞表型发育的贡献包括：(1) 增殖下调，(2) 1 型胶原细胞外基质的生物合成和组织，以及 (3) 该基质的矿化。在初始增殖期添加到分离的成骨细胞中的激素和生长因子可以显着改变随后的分化发育阶段的程序。研究表明，基因表达发生变化是由于：(1) 转化生长因子β (TGFβ1)，它阻止细胞分化及其形成骨组织样结节的能力； (2)糖皮质激素，诱导并加速骨细胞表型的发育； (3) 维生素 D 的活性代谢物 1,25(OH)2D3，它会导致激素对生长和分化产生抑制和刺激作用，这些作用取决于成骨细胞的分化状态。因此，在这些骨细胞表型发育的生理介质存在的情况下，成骨细胞中有效的许多生长和分化关系被改变或消除，从而排除了成熟骨细胞和组织的结构和功能特性的表达。这些发现对于使用激素或生长因子治疗涉及骨骼的疾病具有重要意义。
Osteoblasts in vitro undergo a developmental sequence of growth and differentiation characterized by a stage-specific expression of cell growth and bone-related genes. Our studies show that contributions to development of the osteoblast phenotype include: (1) the down-regulation of proliferation, (2) biosynthesis and organization of type 1 collagen extracellular matrix, and (3) mineralization of this matrix. Hormones and growth factors added to isolated osteoblasts during the initial proliferation period can dramatically alter the subsequent program of developmental stages of differentiation. Studies are presented that demonstrate alterations in gene expression in response to: (1) transforming growth factor beta (TGF beta 1), that prevents differentiation of the cells and their ability to form bony tissue-like nodules; (2) glucocorticoids, which induce and accelerate development of the bone-cell phenotype; and (3) the active metabolite of vitamin D, 1,25(OH)2D3, which results in both inhibitory and stimulatory effects of the hormone on growth and differentiation--effects that are dependent upon the differentiated state of the osteoblast. Thus, in the presence of these physiological mediators of bone-cell phenotype development, many of the growth and differentiation relationships operative in osteoblasts are modified or abrogated, precluding expression of the structural and functional properties of mature bone cells and tissue. These findings have significant implications for use of hormones or growth factors in the treatment of disorders where bone is involved.